Saturday, December 24, 2011

Still Stable

Doctor Visit December 14, 2011
End of the 49th Cycle on the Pomalidomide Study

The news is pretty good, I'd say, though a little confused. IgG dropped to 999, from 1280 mg/dL last month, a whopping 22%, but M-spike remained the same at 1.1 g/dL. As I understand the relationship between IgG and M-spike, this is an impossibility and represents an error (or a tolerance) in at least one of the two tests. I prefer to believe IgG.

On the other hand, if it matters, Lambda light chains popped up from 2.12 to 3.15 mg/dL, a pretty big jump, and now slightly above the top of the reference range. Kappa light chains went up a similar amount though, so the Kappa/Lambda ratio declined only slightly. I suspect a testing anomaly there, and anyway I'm not sure of the significance of light chains in my case.

The only real concern is calcium, which is 10.3 mg/dL, slightly above the top of the reference range, 10.1. The reason for the slightly high calcium is unclear, and worth investigation, because it could indicate a hot spot in a bone somewhere. Or it could indicate poor hydration, which is also believable. Calcium was high last time too, and Dr LH and I had agreed then that if calcium was high again this time she would schedule a skeletal survey for the next trip. It has been scheduled. Meantime, I have no bone pain anywhere and hope that nothing breaks.

As I write this, we are sitting in Mayo Clinic waiting for the new prescription of pomalidomide, for the 50th cycle of the study. When we have it in hand, we're off cross country to a marathon in Delaware. This may not get posted until we arrive there and have a little time.

Note: In fact, it didn't get posted until we finished the marathon, got back home, and caught up on some other things. Now 61 marathons in 42 states since diagnosis.


Some Current Test Results:

Test    Sep 22    Oct 19    Nov 17    Dec 14     Remarks
M-spike g/dL 1.0 1.1 1.1 1.1 \ Tumor marker
IgG mg/dL 1020 1310 1280 999 / Tumor marker
Lambda mg/dL 2.49 2.75 2.12 3.15 L Free light chains
Calcium mg/dL 10.0 10.0 10.3 10.3 High
Creatinine mg/dL 0.9 1.1 1.1 1.1 Kidney, OK
HGB g/dL 14.9 14.6 15.0 15.1 Hemoglobin, OK
RBC M/uL 4.09 4.07 4.18 4.17 Red cells, low
WBC K/uL 6.2 4.8 5.3 4.8 White cells, normal
ANC K/uL 2.60 2.30 1.70 1.90 Neutrophils, normal

Related Links:

My Myeloma     A discussion of my myeloma, not very technical.
My Treatment History Not technical.
My Test Charts Graphic displays of several key test results over time.
My Test Result Table Somewhat technical. Best with a wide browser window.
My Supplement Regimen With links to where I buy them.

Christmas season lunch. All organic:

Tuesday, December 13, 2011

ASH Conference Post # 6 - New Myeloma Therapies

Monday at ASH seems to be the day that most myeloma papers are presented. I spent several hours listening and taking notes.

Dr. Andrzej Jakubowiak

In this study, carfilzomib was combined with Revlimid (Rev) and dexamethasone (dex) for newly-diagnosed patients. Carfilzomib was administered twice weekly, dex decreasing from 40 mg/wk.

After treatment, 100% of patients reached very good partial response (VGPR), which is simply amazing. 79% reached near-complete response (nCR) or better after 12 cycles. Side effects were low. The study is still young, but all patients are still alive. This is a very encouraging study. In the authors' opinion, "These results compare favorably to the best frontline regimens in MM." Who can disagree?

Dr. Paul Richardson

Dr. Richardson pointed out that two previous studies have shown that pomalidomide (pom) is active in patients for whom prior therapies have failed, including both Rev and Velcade. This new study was intended first to find the maximum tolerable dose (MTD), and then to determine progression-free survival (PFS) and overall survival (OS). Patients had lots of prior therapies.

MTD was found to be 4 mg, 3 weeks on, 1 week off.

Pom was studied as a single agent and with dex, and pom/dex was found to be quite superior to Pom alone. To quote my own doctor, "everything works better with dex." PFS was just 4 months for these patients, whose myeloma had become quite resistant prior to this study. OS was short too, but this is no surprise with such heavily pre-treated patients.

Dr. Tomer Mark

Clarithromycin (Biaxin) is an existing approved drug which has been shown to add a significant anti-myeloma benefit when added to the combination of Revlimid and dex. So they tried this with Pom.

Enrolled study patients were resistant to at least three prior therapies, including Rev. The median number of priors was actually five, with many patients over 10. Also, many of the patients were "high-risk," meaning that their myeloma was particularly aggressive.

Despite those odds, almost 70% of patients got a clinical benefit, and 61% were progression-free after almost seven months. This is a very impressive result!

Dr. Yi Lin

Almost ten years ago, Mayo Clinic began a study of a myeloma vaccine made with the patient's own myeloma cells, administered after an autologous stem-cell transplant (ASCT). Today's paper reported the final results. The vaccine provided no advantage in progression-free survival, but did provide a two-year advantage in overall survival. This is counterintuitive, and the subject of ongoing discussion.

Dr. Xavier Leleu

Study compared two different pomalidomide dosages: 4 mg for 21 days of 28 versus 2 mg for 28 of 28 days. Arms were randomized. Most patients were heavily pre-treated (many prior therapies), and many were refractory to Revlimid, or Velcade, or both.

In both arms, about 35% of patients achieved a response. The author concluded that 4 mg 21/28 was superior to 2 mg 28/28. I could not find much justification for that conclusion in the data presented, but he is the doctor and I am most definitely not. The author also stated "This study provides further evidence that pomalidomide has no cross-resistance with lenalidomide ...". I'm not quite certain that his data quite supports that far-reaching conclusion either, but I hope it's true.

Dr. Ravi Vij

Dr. Vij reported on an early study of carfilzomib as a single agent (no dex). Patients had never been treated with Velcade, but had relapsed from as many as four prior treatments. Twelve cycles of carfilzomib were administered. Roughly 60% of patients had a good response.

Carfilzomib has been submitted for FDA approval.

Dr. Paul Richardson

Panobinostat is an oral pan-deacetylase inhibitor which can create defective proteins within a cell (my interpretation). Velcade can prevent the cell from clearing proteins like that, and the two can work together to persuade the cell to die.

Patients were heavily pre-treated, and still the treatment of Panobinostat/Velcade/dex proved effective for about 50% of them.

Perifosine plus Velcade and dex in heavily pre-treated patients, including patients for whom Velcade has failed. Perifosine attacks tumors in a new way, and was known to be synergistic with other drugs. It is an Akt Inhibitor. They wanted to find the MTD, and then the efficacy.

41% of patients achieved a useful response, but some subgroups were much higher. Median OS was 25 months, and 37 months for people who responded well. This is evidence that perifosine can overcome resistance to Velcade in some people. There is now a Phase III trial recruiting.

Dr. Shaji Kumar

MLN9078 ia the first oral proteasome inhibitor to be evaluated for treatment of MM. This study was to determine the maximum-tolerated dose (MTD) of MLN9078 as a single agent. Patients had at least two prior failed therapies.

Conclusion: Dosage has been established, and the drug clearly seems to work, even as a single agent, and caused little or no neuropathy. A doctor near me offered the opinion that MLN9078 shows a great deal of promise and, eventually, might even compare with carfilzomib. If I were on Velcade, getting infusions in a clinic, I would much prefer to take this drug instead, at home, and also avoid the risk of painful neuropathy.

This is the last post from ASH. We're home in Minnesota now, and soon heading off to Mayo Clinic for my regular 28-day checkup and then off to a marathon in Delaware. State # 42 if all goes well.

Monday, December 12, 2011

ASH Conference Post # 5 - How Novel Is Novel?

New Novel Drugs:

As everyone knows (?), the "novel" drugs used in treatment of myeloma are thalidomide, lenalidomide (Revlimid), and bortezomib (Velcade). This trio has revolutionized the treatment of myeloma in the recent few years, probably almost doubling the survival time of newly-diagnosed myelomiacs.

But there are more new drugs coming, lots of them, with carfilzomib and pomalidomide leading the pack. From an outsider's view, those two are about equally potent and equally close to FDA approval. Both are hugely successful in treating myeloma, often even in patients for whom the novel drugs have failed. Both have successful Phase II trials to recommend them, but neither has a Phase III trial.

Onyx has submitted carfilzomib for FDA review and requested priority review. The FDA has accepted it for review, but declined priority review, so it could take until summer. So far. Celgene has not yet submitted pomalidomide for review, but according to one source, may submit it by the end of the month.

These two could be FDA approved within a year. Then which are the novel drugs? Do we have a cast of five, or two neo-novel drugs and three post-novel drugs? I'm sure someone smarter than me will figure out how to classify them.

Pomalidomide Study:

Long-term Outcomes of Pomalidomide and Dexamethasone in Patients with Relapsed Multiple Myeloma: Analysis 4 Years After the Original Cohort

This is the study that I am in. I started taking pomalidomide three years and nine months ago. Most of the patients enrolled in the study were sicker than me, in Stage 2 or 3, where I was in Stage 1. Many had lots of prior failed therapies. Nevertheless, half of the standard-risk patients (like me) remained progression-free for at least 18 months, with a 2-year survival of 85%. Twelve of the original 60 patients are still on the drug - I am one of those, about to complete Cycle 49. I can stay on it as long as it works. Here's hoping.

Cornucopia of New Therapies:

Dr. Robert Orlowski, a well-known myeloma expert, used that phrase Friday night. I love it and will definitely quote him at my next support group meeting.

I get an overwhelming sense of hope at this conference. Things are really happening. Just today I counted 80 posters on myeloma alone. In the three days of poster talks, I suppose there will be 200 to 250, just on myeloma, each representing serious scientific research. Not all, maybe even not most, will be investigations of new treatments, but many are. All of the papers advance the science significantly.

Treatment options are expanding almost daily. There is SO much hope this year - stay alive for it.

Sunday, December 11, 2011

ASH Conference Post # 4

At the Conference of the American Society of Hematology (ASH), there is a huge room filled with rows and rows of poster boards, showing posters on both sides. Hundreds (thousands?) of posters, and they are changed every day to a new set of posters. Each poster shows the work of a researcher or perhaps an entire research center.

I walk through those in a bit of a daze, with no idea which poster might represent a future treatment. Some posters show the results of long studies providing valuable information, and some are just good ideas that seem to work in concept but eventually may not work out. But one of those good ideas caught my eye, titled Myeloma Exhibits Dependence on Atypical Glucose Transporters: Targeting MCL-1 Through GLUT4 Inhibition.

I'm not a medical researcher and most of the medical terms mean nothing to me, of course, but the story here is that it may be possible to starve the sugar-hungry myeloma cells by finding a drug that targets GLUT4, one of several glucose transporters. When that is done, the cells die. To prove the concept, they used an FDA-approved HIV drug called ritonavir, which inhibits GLUT4 as a side effect of other actions.

The researcher, Mala Shanmugam, PhD, of Northwestern University, believes that it might be possible to develop a drug which would target GLUT4 directly.

Here is yet another avenue of attack on myeloma. We've seen a "cornucopia of new therapies" already, and there are more on the horizon, including this one. There is a LOT of hope here - please do stay alive for it!

Typical poster, one of zillions:

Friday, December 9, 2011

ASH Conference Post # 3 - Myeloma Questions and Controversies: New Developments in 2011 that Impact Diagnosis, Prognosis and Treatment

The International Myeloma Foundation (IMF) presented their usual excellent review of current clinical practice in myeloma. Most of the attendees were hematologists. 20% of the audience managed more than 50 patients annually, and another 30 percent managed more than ten.

Dr. Vincent Rajkumar:

Diagnosis and and Prognosis:

The doctor who suspects myeloma should do SPEP, immunofixation, immuglobulins, and free light chains. All of them are necessary, because none of those tests will catch all presentations of myeloma.

Doing a free light chain test on urine eliminates the need for the 24-hour urine test.

Myeloma is not in Stage 1 (active) until at least one of the CRAB symptoms is present. Calcium, Renal (kidney), Anemia, or Bone. But if the percentage of plasma cells in the bone marrow is high, say 60%, the disease should be treated as if it is active myeloma. All such patients will progress.

Prognosis depends on tumor burden, aggressiveness, patient performance (age), and other health factors, such as kidney health. Tumor aggressiveness is usually estimated by cytogenetic tests. Response to initial therapy is also an important prognostic factor, though sometimes a patient who responds most rapidly will also have the fastest relapse.

75% of all myeloma patients are normal-risk and have a median survival of 7-10 years or more. High risk, defined by cytogenetics, have a median survival of 2-3 years.

Dr. Jesus San Miguel:

Asked if a cure is possible in MM: The audience was evenly divided. How important is CR?: Nearly everyone thought it was important. He believes that the better the quality of response, the longer the survival.

Q: If a patient achieved a CR on the transplant conditioning regimen, should the transplant still be done? 73% of the doctors in the audience said yes. Hmmm.

Trials are now addressing the question of transplant upfront versus transplant at the time of relapse from initial therapy.

He believes that intensive frontline therapy, such as SCT, is preferable to a more gentle treatment with one therapy at a time. Your blogger knows that this is a hot topic of controversy.

Can novel or intensive approaches overcome high-risk prognosis? 71% said YES! He said they were wrong. The outcome can be improved, but the prognosis cannot be overcome. Trick question? Maintenance therapy after SCT can also improve the outcome, but high-risk patients will not achieve the same OS as standard-risk.

Allogeneic transplants, using stem cells from a donor instead of the patient's own stem cells, may be an answer for patients who achieve CR and then relapse almost immediately. A study is needed. Last thought: Myeloma is not a single disease. Individualized treatment is needed.

There is no problem giving a transplant to a patient between 65 and 70 if the patient is sufficiently fit.

Dr. Antonio Palumbo:

Treatments for elderly patients. Options:

The new combination of Melphalan/Prednisone/Velcade got the most votes for initial therapy. The actual patient got a "perfect" CR. Now what? 53% say complete six cycles of MPV. He actually was given nine. What now? 35% said no maintenance, others split among different types of maintenance. How long do we continue it? (6 mo to 24 mo, or until progression or unacceptable toxicity). Doctors chose maintenance until progression or until unacceptable toxicity.

He believes in aggressive therapy up front, while the elderly patient is still strong, and then maintenance to maximize progression-free survival (PFS) and overall survival (OS).

Dosage may have to be reduced for elderly patients, because therapy may be more toxic to them. Once weekly should be the standard for Velcade, not twice. Is he still giving Velcade twice a week to other patients? Ouch, says your blogger. Subcutaneous injection was not mentioned but may be preferable, also says your blogger.

Elderly patients who achieve CR and have no other serious ailments, have a 70% chance of survival to five years.

MPT is the current standard of care. He talked a lot about melphalan, and thinks that two- and three-drug combinations with melphalan are the standard of care for the elderly.

For unfit patients, 37% of myeloma patients, the "standard" therapies are often too toxic. He gave a chart of reduced dosages, and it was clear that the practitioner is left to make the choices.

I'm glad he is not my doctor. I think that doctors in the USA are more likely to offer the novel therapies to elderly patients like me, rather than sticking them with elderly therapies.

Phillippe Moreau:

Consolidation and Maintenance after transplant, for young (less than 65) patients

The audience voted on several maintenance options, including none at all, and most chose consolidation plus maintenance. Consolidation is usually a brief, fairly aggressive therapy given after the SCT, to further reduce the tumor burden, and maintenance is a long-term treatment, often using a small dose of a single therapeutic agent such as Revlimid or Velcade.

The audience was asked what is the best available consolidation therapy? One of the choices was a second SCT. Result: The audience thought that a triplet therapy such as Velcade/thalidomide/dexamethasone (VTD) or Revlimid/Velcade/dex (RVD) was best. Bottom line: No current studies exist for guidance.

After two cycles of consolidation, what maintenance is appropriate? Possible answers included none, Revlimid, or Velcade. The audience chose Revlimid maintenance.

Recent studies show that Revlimid maintenance offers a substantial improvement in progression-free survival, and one study also shows an improvement in overall survival. Thalidomide may be a different story - no study shows a long-term improvement in overall survival with thalidomide maintenance, but most show toxicity in the form of peripheral neuropathy.

Conclusions: Consolidation questions require trials. Maintenance looks good but may not result in improved overall survival.

Dr. Robert Orlowski:

What about patients who have tried most available therapies?

Patient example: Many many failed therapies. Dr Orlowski presented eight possible treatment choices. The audience chose carfilzomib with Revlimid and Dex. He said that a combination including pomalidomide was second choice, though I didn't see that on the list of choices.

He used the term "A Cornucopia of New Drugs," including the "novel" drugs, which are now standard treatment, and including drugs that have new and different mechanisms of action. There is even an investigational oral proteasome inhibitor, which works like Velcade but can be taken at home.

He made quick mention of many new agents such as perifosine and vorinostat. Efficacy of proteasome inhibitors can be improved by adding HDAC inhibitors. Elotuzomab is a synthetic monoclonal antibody which shows promise.

We don't really know why Revlimid stops working for many patients.

Rev/Dex or Vel/Dex remain the standard of care. However, novel agents like carfilzomib and pomalidomide are "on the cusp" of availability. More-novel agents like ARRY530 may be on the way. Cyclophosphamide is an old drug that has become new again in combination with newer agents.

We need research telling us why myeloma becomes resistant to therapies. Then we can tailor treatment to the specific myeloma.

That was the end of the session. If you got this far, you should give yourself a little treat - not an unhealthy one, mind you, but maybe a modest piece of dark chocolate, or a few dried apricots, or perhaps a short nap. You deserve it.

ASH Convention Post # 2 - Current Clinical Controversies and Future Research Priorities for the Treatment of Multiple Myeloma

That is the title of my first symposium at the conference of the American Society of Hematology (ASH), Friday, December 9, 2011, three hours. It seemed to be intended for clinical practitioners - doctors who treat myeloma patients and need to stay up to date in this rapidly-changing field.

I attended with all of the attention and understanding of an electrical engineer - or lawyer - doesn't matter, I'm not a doctor. The session was a flood of information and I was not able to keep up, which is on me, not the presenters. With that disclaimer, here is what I got out of it:

Dr. Paul Richardson, Dana-Farber, Chairperson of the Symposium:

Frontline treatment still divides patients in to two groups - transplant-eligible or not eligible.

Revlimid/Velcade/Dexamethasone (RVD) has proven to be very effective. Cyclophosphamide/Velcade/Dex may be just as good as a frontline therapy, but all four drugs together were not as good because of toxicities. Cyclophosphamide (Cytoxan) is an alkylating agent like melphalan. "Frontline" means the first therapy for a newly-diagnosed patient.

Almost every myeloma patient relapses, whatever the therapy. With good front-line therapies now, the real challenge is to treat patients with relapsed and refractory disease. His slide contained at least 30 different combinations of drugs available to the practitioner. Doxorubicin (Doxil) has become an important option, in combination with other novel drugs, although the supply is questionable.

Ongoing studies add a number of new agents, or agents new to myeloma, to the existing drug combinations.

In one specific case involving an 84-year-old woman, the opinion of the doctors in the audience about the importance of achieving a complete response (CR) or very good partial response (VGPR) varied widely. The largest group thought it was "somewhat" important, but some thought it wasn't important at all, and some thought it was very important.

Question from the floor: Why do we treat the elderly different from young people? This patient had been treated with a melphalan combination, but Dr. Richardson responded that he would not have treated her differently from a younger patient, and would have given her the same front-line therapy, but tailored to her tolerance of it.

Dr. Philip McCarthy, Jr.:

Maintenance Therapy Post-transplant

Zometa is preferable to Aredia and other bisphosphonates because it does seem to have a modest anti-myeloma effect.

A recent study using thalidomide as a maintenance after stem-cell transplant (SCT) did not show much benefit for progression-free survival (PFS) or overall survival (OS).

Another study has shown a very significant benefit from Velcade maintenance after SCT.

Revlimid maintenance has shown significant PFS, and at this point in the study, one of two studies is also showing a significant OS.

Conclusion: Revlimid is appropriate for prolonging time to progression (TTP), event-free survival (EFS), and overall survival (OS). Velcade as well. Also, to a lesser degree, Zometa.

Case: 72-year-old widowed woman, working in doctor's office. Scapular pain. IgA myeloma. Four therapies were presented to the group, which voted with tiny handheld wireless voting pads. The the top choice was a melphalan/prednisone/thalidomide combination, and the second choice a Rev/Velcade/dex combination. Blogger's comment: Why do doctors persist in giving OLD therapies to OLD people, when novel therapies are proven to be better? There seems to be incredible inertia in the medical field, especially among clinicians.

Comment by a panel member: PET/CT, though expensive, can be helpful in some cases, but not so much when other diagnostics already show active disese.

Maria-Victoria Mateos, M.D., Ph.D.:

Discussion of two classes of novel agents: Proteasome inhibitors (e.g. Velcade) versus immunomodulatory agents (e.g. Rev/thal). In both classes, new agents are being introduced and may help patients for whom first-line therapy has failed.

Carfilzomib/Rev/Dex produced a very high rate of complete or very good response. Several other proteasome inhibitors are coming along.

Pomalidomide seems to provide a benefit to 25-34% of patients for whom Rev and thalidomide are no longer of benefit. There are also combinations of pomaldomide with clarithromycin and other agents.

Bottom line: Both classes benefit from continuing research and innovation.

Andrzej J. Jakubowiak, M.D., Ph.D.:

Dr. Jakubowiak discussed novel mechanisms for overcoming myeloma's resistance to current therapies. This went very fast, but is also very exciting. He mentioned nine different drugs which have shown benefit when used in combination with Revlimid or Velcade, and a tenth was mentioned by another panelist.

Drugs synergistic with Velcade: Elotuzumab, Perifosine, Vorinostat, Panobinostat, more.

Synergistic with Revlimid: Vorinostat, panobinostat, more.

Also the efficacy of the traditional therapy melphalan/prednisone/thalidomide (MPT) is improved with Vorinostat or panobinostat. Resistance to Rev/Velcade/Dex (RVD) can also be overcome with Vorinostat.

Plitidepsin suppresses proliferation and anti-apoptosis genes. In other words, it affects the genes which cause the myeloma cell to grow rapidly, and the genes that prevent the cell from dying when it knows that it's goofy and should die. An engineer's view. That's really cool stuff.

Elotuzumab works by yet another mechanism, and has shown a significant benefit in combination with both Revlimid and Velcade.

Bottom line: Some of these new therapies are very promising, when used in combination with existing drugs, and ongoing trials will tell us which will provide the most help and for whom.

My Take:

I attended ASH two years ago, when Revlimid and Velcade were relatively new and were the subject of every talk. Now they are unquestionably the standard, and the buzz is about new agents for use in combination with them, to make them work better and longer.

Thursday, December 8, 2011

ASH Convention Post # 1

Flying into San Diego, you get a spectacular crystal-clear view of the city's downtown and Balboa Park, not to mention San Diego Bay, just in the last minute as the plane is about to touch down. If the wind is from the west, that is, otherwise the plane will land from the west and the view will be different.

We're ensconced in the San Diego Sheraton, and right now the hotel is trying to figure out how connect three computers in one room. No WI-Fi in this place yet! But if you are reading this post, it means that they got it figured out.

I'll be posting about myeloma issues as often as I can during the conference, so do stay tuned. I'll also be leading a fun run at 1:00 pm Saturday, and will be involved in other publicity events for Team Continuum.

If you have a Facebook account (who doesn't?) and haven't done it yet, please go to and "like" it, because a sponsor will contribute $5.00 to Team Continuum and it won't cost you anything more than a few seconds and a couple of clicks.

View from our hotel room balcony. Don't feel sorry for us:

Friday, December 2, 2011

CNN Story Good News Bad News

Good News:

My little story about cancer man running marathons is on Headline News today. I've seen it twice, at about 9:13 and 10:13 am.

Bad News:

A longer version was scheduled for the Sanjay Gupta M.D. show, at 6:30 am this Saturday and Sunday. It has been slipped one week, however, because Dr. Gupta will focus on AIDS this weekend. So it should appear December 10 & 11, both days, at 6:30 am CST. Maybe?

Online Version:

It is already available online at CNN Blogs. This version also includes an article which I wrote.